A Systematic Review for Estimation of HTLV-I Infection in the Blood Donors of Iran

HTLV-I infection is a worldwide health problem and approximately 15–20 million persons are estimated to be infected with this infection (1). High HTLV-I seroprevalence rates in the general population or specific groups such as blood donors, have been reported from southwest of Japan, Caribbean basin, South America, Sub-Saharan Africa, and northeastern Iran (1,2). 
 
Although most infected people remain asymptomatic, the virus is associated with exceptionally severe diseases, such as adult T-cell leukemia/lymphoma (ATL), and HTLV-I-associated myelopathy/tropical spastic paraparesis (HAM/TSP) (3). HTLV-I infection could transmit from mother to child, predominantly through breastfeeding, via sexual intercourse, and parenteral transmission by transfusion of infected cellular blood products or sharing of needles and syringes (1,4). 
 
Presence of HTLV-I infection was reported in 1990 among the Jews emigrated from Mashhad, northeast of Iran (5), and then some patients with ATL were indentified in Mashhad who were seropositive for HTLV-I (6). In later studies, the rate of HTLV-I infection in Mashhad was reported 3% in general population (7) and about 2% in blood donors (8) in 1996. There were some small to large scale epidemiological studies that have reported the prevalence of HTLV-I infection in blood donors from various regions of the country. The widest survey has been conducted by Rezvan et al. in 21 regional blood centres in 1996. This study reported a 0.29% rate for HTLV-I infection in total serum samples; 1.97% among Mashhadi blood donors, and zero to 0.5 percent in other centres (8). Moreover, later surveys in several regions of Iran reported different rates of the infection in blood donors. Nevertheless, there is no overall estimation of the infection in the country. This study conducted to accurately estimate the prevalence of HTLV-I infection in the Iranian blood donors through a comprehensive systematic review of literature and evidences.


valence in th
Iranian blood donors.Method: All cross-sectional studies which had reported the prevalence of HTLV-I infection in the Iranian blood donors in both English and Persian languages until August 2011 were adopted.The inclusion criteria were proper sampling methods, adequate sample size, and valid measurement methods.The overall prevalence rate was estimated using meta-a alysis method as well as survey data analysis methods.Results: From 843 electronic searched citations, and 245 surveys found in gray literatures, 13 studies met the inclusion criteria.They were from seven provinces including Razavi Khorasan (0.38-1.16%),West Azarbaijan (0.34%), Ilam (0.21%), Hormozgan (0.18%), Alborz (0.11%), South Khorasan (0.04%), and Bushehr (0.01%).The overall estimation of the HTLV-I prevalence rate in Iranian blood donors was 0.119% (95% confide ce interval (CI): 0.050-0.287percent).Conclusion:It is concluded that HTLV-I infection in Iranian blood donors is considerably prevalent.It is highly recommended to continue prevention programs such as strict blood screening.(5) , and then some patients with ATL were indentified in Mashhad who were seropositive for HTLV-I(6).In later studies, the rate of HTLV-I infection in Mashhad was reported

Introduction

HTLV-I infection is a worldwide health problem and approximately 15-20 million persons are estimated to be infected with this infection (1) .High HTLV-I seroprevalence rates in the general population or specific groups such as blood donors, have been reported from southwest of Japan, Caribbean basin, South America, Sub-Saharan Africa, and northeastern Iran (1,2) .

Although most infected people remain asymptomatic, the virus is associated with exceptionally severe diseases, such as adult T-cell leukemia/lymphoma (ATL), and HTLV-I-associated myel

cal spastic par
paresis (HAM/TSP) (3) .HTLV-I infection could transmit from mother to child, predominantly through breastfeeding, via sexual intercourse, and parenteral transmission by transfusion of infected cellular blo

products or sha
ing of needles and syringes (1,4) .

Presence of HTLV-I infection was reported in 1990 among the Jews emigrated from Mashhad, northeast of Iran 3% in general population (7) and about 2% in blood donors (8) in 1996.There were some small to large scale epidemiological studies that have rep

TLV-I infection in bloo
donors from various regions of the country.The widest survey has been conducted by Rezvan et al. in 21 regional blood centres in 1996.This study reported a 0.29% rate for HTLV-I infection in total serum samples; 1.97% among Mashhadi blood donors, and zero to 0.5 percent in other centres (8) .Moreover, later surveys in several regions of Iran reported different rates of the infection in blood donors.Nevertheless, there is no overall estimation of the infection in the country.This study conducted to accurately estimate the prevalence of HTLV-I infection in the Iranian blood donors through a comprehensive system

ic review of literature and evidences.


Met
ods


Study Question

The interested outcome was the presence of HTLV-I antibody in blood samples of the Iranian blood donors, based on any blood tests or even if laboratory tests are not identified clearly, until August 2011.


Search Strategy

"HTLV" was used as a key word anywhere in the text for searching national electronic databases and websites."HTLV" anywhere in the text (all fields), and "Iran", "Iranian" or "Iranians" in the title, subject terms (keywords

or affiliation w
re also used for searching other databases.


Electronic Databases

Seventeen electronic bibliographic databases and publishers of the health and biological sciences were searched.These included: BioMedCentral, BMJ Journals, Cochrane Library, Directory of Open Access Journals (DOAJ), Ebscohost, Emerald Journals, Google Scholar, MD Consult, OvidSP, Oxford Journals, ProQuest, PubMed, Sci-enceDirec

Scopus, SpringerLink
Contemporary, Web of Knowledge (ISI), and Wiley InterScience Journals.Moreover, all seven Iranian databases of literatures including Iranian Research Institute for Information Science and Technology (IranDoc), Iranian Database of Medical Sciences Papers (IranMedex), Iranian Database of Publication (Magiran), Global Medical Articles Library (Medlib), National Management System

and Technology
Information (ISNet), the Regional Information Centre for Science & Technology (RICeST), and Scientific Information Database (SID) were investigated.


Gray Literature Search

All of Iranian medical universities' websites as well as Iranian databases such as IranDoc, ISNet, and RICeST were searched or reports of scientific congresses, research projects, and dissertations.Also libraries of faculties of medicine from Mashhad University of Medical Sciences (MUMS), and Islamic Azad University, Mashhad branch, were investigated for their thesis archives.National reports from Centre for Disease Control (CDC) of the Iranian Ministry of Health, and the Iranian Blood Transfusion Organization (IBTO) websites were also investigated.Finally, cited items of identified studies were screened.


Critical Appraisal and Selection of Studies

All titles and abstracts were screened, and relevant citations were reviewed thoroughly and checked for eligibility criteria to include the studies in the analysis.The inclusion criteria were all cross-sectional surveys that have employed appropriate sampling methods, had adequate sample size (more than 200 individuals), and provided esti

tion of prevalence of HTLV-I
infection in blood donors using valid measurement methods in both English and Persian languages.


Data Extraction

The selected and included citations were reviewed, and the findings were extracted to a sheet.The extracted data was first author, year of the study, province/city of the study, sampling method, sample size, name of the kits and methods used for HTLV antibody detection, mean and standard deviation of subjects' age, percentage of male subjects, and total and sex-related HTLV-I point prevalence.


Statistical Analysis

The total and sex-related point prevalence of HTLV-I infection was recalculated according to the number of infected cases and total observations reported in each study.Binomial 95% CI was computed using EPI 6.0 software (CDC, USA).Meta-analysis method using random effect model was used based on the results of heterogeneit test (Cochrane Q) with significance set at P< 0.05.


Results


Search Result

175 relevant nonduplicate citations of all 843 electronic searched citations were found, of which 17 studies discussed seroprevalence of HTLV-I in Iranian blood donors (8-24)   .Two studies were excluded due to overlapping samples (12,15).

In gray literature search another 245 surveys including 104 published in abstract books of congresses, 64 researc

reports,
and 77 theses were found, of which seven nonoverlapping studies were with subjects in blood donors (25)(26)(27)(28)(29)(30)(31) .Access to data of three studies was not possible in spite of requesting from related institutes (29)(30)(31) .Moreover, one relevant study published in Persian found from backward citations (32) but had overlap with another English paper (8) .On the other hand, no relevant data was found in searching organizations reports.After excluding studies with samples that wer not representative of the target population (11,18,24) or with inadequate samples size (13,28) and/or studies which did not use confirmatory tests (13,16) , finally 13 studies were selected.The detailed search process is demonstrated in Figure 1.


HTLV-I Infection Prevalence

Mashhad, the capital city of Razavi Khorasan province, has still remained as the most prevalent area for HTLV-I infection; however, the infection rate has fallen from 1.16% in 1997-2000 (14) to 0.38% in 2008-2009 (22) .Urmia, the c

ital city o
West Azerbaijan province, has the second place, and HTLV-I infection prevalence has reported as high as 0.34% (19) .Prevalence of the infection among blood donation volunteers in Karaj, the capital city of Alborz province, and Hormozgan and Ilam provinces ranges from 0.11 to 0.21 percent (20,21,27) .The lowest prevalence rates were seen in south Khorasan (0.042%) (23) and Bushehr (0.013%) (17) .Prevalence of the infection according to the sex was verified or calculable only in six surveys.Except for one study (17) , the infection rate in female blood donors was 2 to 6 times higher than males (Table 1).

From six studies conducted in Mashhad, the latest survey included in meta-analysis (17) and a study performed in 21 provinces was excluded (8) .According to data from seven studies, point estimation for HTLV prevalence in Iranian blood donors was 0.119% (95% CI: 0.050-0.287percent).(Figures 2 & 3).By using heterogeneity test, a significant variation was found between the studies (Q= 151.13, df=6, P<0.001, I-squared= 96.03%).


Studies

Thirteen relevant studies with a total of 1,091,361 subjects were found of satisfactory quality (8)(9)(10)14,17,(19)(20)(21)(22)(23)(25)(26)(27) . All included surveyswere cross sectional studies conducted on Iranian blood donors from 1996 to 2009 with sample size ranging from 960 to 243,856 (Table 1).One study had been conducted in the regional blood centres of 21cities in the country (8) and six were from Mashhad covering the years from 1997 to 2000 (9,14) and 2004 to 2009 (10,22,25,26) .

The age of the subjects was only determined in five studies (9,10,19,20,27) which was between 17 and 65.Sex distribution of subjects was reported in nine studies (9,10,17,19,20,22,23,25,27) , 79 to 94 percent of the subjects were males.All studies had used ELISA tests by several HTLV detection kits (such as Biomeriux, Diapro, Genlab, MP Diagnostics, Organon, Ortho, and ZeptoMetrix) for primary screening, and western blot by some HTLV-blot kits, mainly Genlab, with or without PCR as confirmatory t sts.


Discussion

This review for estimating the overall prevalence of HTLV-I infection in Iranian blood donors indic